Although treatments in animal models for HD have proven successful, and several clinical trials are underway in persons with manifest HD, there currently exists no methodology in which to test experimental therapeutics prior to diagnosis of manifest motor disease. The Predict-HD study is designed to provide essential methodology for the initiation of preventive clinical trials in Huntington's disease (HD). Early identification of neurological disease is imperative so that intervention using protective, gene therapy, and regenerative strategies can be initiated at high levels of life quality and prior to the occurence of irreversible cellular injury. The Predict-HD study has successfully recruited nearly 500 healthy participants who had previously undergone genetic testing for the HD expansion. Annual measures of brain imaging and cognitive performance are obtained in concert with other demographic, clinical and genetic information. Findings already suggest a remarkable convergence of the first detectable decline in brain morphology, motor skill, and cognitive ability at about 15 years prior to traditional motor diagnosis. This is notably earlier than had generally suspected and represents a major advance in our understanding of HD. With completion of the requested 3-year continuation of the Predict-HD study we will have longitudinal observations that allow us to: 1) Test and refine the model of early HD changes suggested by our baseline data; 2) Determine which measures of functional decline are concurrent with measureable brain morphology changes; and 3) Better understanding of the relationships among striatal and cortical changes, DNA repeat length, and clinical phenotype in HD. Completion of Predict-HD will result in a methodology and a cohort that can be readily applied to presymptomatic treatments as they become available. In addition to the contribution this will make towards early intervention in HD, our findings are likely to improve our understanding of the functional pathophysiology of other neurodegenerative and genetic illnesses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS040068-05
Application #
6930299
Study Section
Special Emphasis Panel (ZNS1-SRB-K (19))
Program Officer
Oliver, Eugene J
Project Start
2000-04-01
Project End
2008-08-31
Budget Start
2005-09-21
Budget End
2006-08-31
Support Year
5
Fiscal Year
2005
Total Cost
$4,359,483
Indirect Cost
Name
University of Iowa
Department
Psychiatry
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Wesson, Melissa; Boileau, Nicholas R; Perlmutter, Joel S et al. (2018) Suicidal Ideation Assessment in Individuals with Premanifest and Manifest Huntington Disease. J Huntingtons Dis 7:239-249
Hong, Yi; O'Donnell, Lauren J; Savadjiev, Peter et al. (2018) Genetic load determines atrophy in hand cortico-striatal pathways in presymptomatic Huntington's disease. Hum Brain Mapp 39:3871-3883
Carlozzi, Noelle E; Boileau, Nicholas R; Perlmutter, Joel S et al. (2018) Agreement between clinician-rated versus patient-reported outcomes in Huntington disease. J Neurol 265:1443-1453
Fritz, Nora E; Boileau, Nicholas R; Stout, Julie C et al. (2018) Relationships Among Apathy, Health-Related Quality of Life, and Function in Huntington's Disease. J Neuropsychiatry Clin Neurosci 30:194-201
Hong, Sungmin; Fishbaugh, James; Gerig, Guido (2018) 4D CONTINUOUS MEDIAL REPRESENTATION BY GEODESIC SHAPE REGRESSION. Proc IEEE Int Symp Biomed Imaging 2018:1014-1017
Lai, Jin-Shei; Goodnight, Siera; Downing, Nancy R et al. (2018) Evaluating cognition in individuals with Huntington disease: Neuro-QoL cognitive functioning measures. Qual Life Res 27:811-822
Carlozzi, Noelle E; Hahn, E A; Frank, S A et al. (2018) A new measure for end of life planning, preparation, and preferences in Huntington disease: HDQLIFE end of life planning. J Neurol 265:98-107
Carlozzi, N E; Schilling, S; Kratz, A L et al. (2018) Understanding patient-reported outcome measures in Huntington disease: at what point is cognitive impairment related to poor measurement reliability? Qual Life Res :
Ghayoor, Ali; Vaidya, Jatin G; Johnson, Hans J (2018) Robust automated constellation-based landmark detection in human brain imaging. Neuroimage 170:471-481
Long, Jeffrey D; Lee, Jong-Min; Aylward, Elizabeth H et al. (2018) Genetic Modification of Huntington Disease Acts Early in the Prediagnosis Phase. Am J Hum Genet 103:349-357

Showing the most recent 10 out of 172 publications